ML29255 Neoadjuvant Vemurafenib and Cobimetinib Melanoma

• Status: Withdrawn
• Trial end date: 2018-02-24
• Target enrollment: 0
• Participant gender: All

Summary

Neoadjuvant Vemurafenib and Cobimetinib in BRAF V600 Mutant Stage IIIB-C Melanoma

• To evaluate the overall radiological complete response rate in patients with stage IIIB/C melanoma after 8 weeks of neoadjuvant vemurafenib and cobimetinib

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Inova Health Care Services
• Collaborator: Genentech, Inc.
• Treatments: Vemurafenib

Criteria

Patients will be included in the study based on the following criteria:

• Signed informed consent

• Histologically confirmed, palpable, regional lymph node metastatic melanoma ≥ 1.5cm (stage IIIB-C; N1b-3) either at initial presentation or at regional lymph node recurrence considered surgically resectable at baseline by the treating medical oncologist and surgical oncologist

• Patients with intransit or satellite metastases with lymph node involvement are allowed if considered surgically resectable at baseline

• Measurable disease per RECIST 1.1

• Melanoma must be documented to contain a BRAFV600 mutation by a CLIA approved laboratory

• No evidence of distant metastasis

• Age ≥ 18 years

• ECOG performance status ≤1

• Adequate bone marrow function as indicated by the following:

• ANC greater than 1500/µL

• Platelets ≥ 100,000/µL

• Hemoglobin greater than 9 g/dL

• Adequate renal function, as indicated by creatinine ≤1.5 x the upper limit of normal (ULN)

• Adequate liver function, as indicated by bilirubin ≤1.5 x ULN

• AST or ALT less than 3 x ULN (patients with documented liver metastases: AST and/or ALT ≤5 x ULN)

• Able to swallow pills

• Negative serum pregnancy test within 7 days prior to commencement of dosing in premenopausal women. Women of non-childbearing potential may be included without serum pregnancy test if they are either surgically sterile or have been postmenopausal for ≥ 1 year.

• Fertile men and women must use an effective method of contraception during treatment and for at least 6 months after completion of treatment as directed by their physician. Effective methods of contraception are defined as those which result in a low failure rate (i.e., less than 1% per year) when used consistently and correctly (for example implants, injectables, combined oral contraception or intra-uterine devices). At the discretion of the Investigator, acceptable methods of contraception may include total abstinence in cases where the lifestyle of the patient ensures compliance. (Periodic abstinence [e.g., calendar, ovulation, symptothermal, post-ovulation methods] and withdrawal are not acceptable methods of contraception.)

• Willing and able to undergo biopsy for research purposes

• Willing and able to sign informed consent

Exclusion Criteria:

• Had prior radiotherapy at lymph node basin

• Prior treatment with BRAF inhibitor or MEK inhibitor

• Active infection

• Pregnant, lactating or breast feeding women

• Concomitant malignancies or previous malignancies within the last 5 years, with the exception of adequately treated basal or squamous cell carcinoma of the skin or carcinoma in situ of the cervix.

• History of malabsorption or other condition that would interfere with absorption of vemurafenib or cobimetinib

• Any underlying medical or psychiatric condition, which in the opinion of the Investigator will make the administration of vemurafenib and cobimetinib hazardous

• Unwillingness or inability to comply with study and follow-up procedures.

• The following foods/supplements are prohibited at least 7 days prior to initiation of and during study treatment:

• St. John's wort or hyperforin (potent cytochrome P450 CYP3A4 enzyme inducer)

• Grapefruit juice (potent cytochrome P450 CYP3A4 enzyme inhibitor)